The overall goal of the proposed research is to develop our fundamental knowledge of the basic mechanism(s) by which mononuclear phagocytes regulate proliferation of various normal cell types. In addition, the capacity of macrophage-derived factor(s) to modulate the proliferation of transformed cells will be investigated. We plan to extend, in two general directions, our preliminary findings that macrophages and macrophage-like cell lines elaborate specific soluble factor(s) that can cause quiescent fibroblasts to initiate traverse of the cell cycle. We have operationally defined this monokine(s) as a competence factor, similar in its action to other known competence factors (platelet-derived growth factor and fibroblast growth factor) but biochemically distinct from both. One limb of the research will be focused on purification of this monokine and characterization of its biochemical/biophysical properties and biological activities. Purification will also allow us to develop specific antisera using rabbits and/or monoclonal antibodies using rat-mouse hybridomas. In addition to establishing the range of cell types sensitive to this monokine, specific molecular changes induced in fibroblasts will be examined. Our aim is to compare this monokine with other known growth factors as an initial step in using these as probes to dissect the cellular events associated with proliferation. The thrust of the second limb of research will be to ascertain those conditions that evoke production and secretion of this monokine from mouse macrophages isolated in vitro. Macrophages stimulated step-wise to each of 4 operationally-defined levels of activation will be assayed for changes in growth factor elaboration. The results obtained should provide a foundation for definitive studies on the relation of macrophage-derived competence factor production in vivo to lesions characterized by mononulcear phagocyte accumulation, extensive fibroplasia and collagen deposition.